Woodhouse-Sakati syndrome ... (Woodhouse-Sakati syndrome) - Gen DCAF17
Syndrome Woodhouse-Sakati (WSS) is a process that mainly affects the endocrine system and the nervous system of the organism. Signs and symptoms of this condition, which gradually worsens, vary widely among affected individuals, even within the same family.
People with Woodhouse-Sakati syndrome produce abnormally low amounts of hormones that direct sexual development (hypogonadism), which usually becomes evident during adolescence. Without HRT, affected individuals do not develop secondary sexual characteristics, such as pubic hair, breast growth in women, or a deeper voice in boys. Women with Woodhouse-Sakati syndrome lack functional ovaries and instead may have streak gonads. The uterus can also be small or absent in affected women. In addition, affected males produce little or no sperm. As a result, people with Woodhouse-Sakati syndrome are usually infertile.
In the early 20s, nearly all affected individuals with diabetes mellitus and hypothyroidism. People with Woodhouse-Sakati syndrome also suffer from hair loss that begins in childhood and gradually worsens, often leading to total alopecia in adulthood. In addition, some affected people have additional characteristic facial features, including an elongated, triangular face, hypertelorism and a prominent nasal bridge.
More than half of people with Woodhouse-Sakati syndrome manifested neurological problems. Dystonias are frequent in individuals affected and usually begin in adolescence or early adulthood. These abnormal movements may include muscle twitching or twisting specific parts of the body, like an arm or a leg. Other neurological features may include dysarthria, dysphagia, mild mental retardation and sensorineural hearing loss. Hearing problems develop after a person has acquired spoken language, usually in adolescence. In some affected individuals they were detected abnormal iron deposits in the brain. Therefore, the syndrome Woodhouse-Sakati is sometimes classified as a group of disorders that are called neurodegeneration brain iron accumulation (NBIA).
This process is due to mutations in the gene DCAF17 (DDB1 and CUL4 associated factor 17), located on the long arm of chromosome 2 (2q31.1), encoding a protein whose function is unknown. This gene is expressed in various organs and tissues in the body, including the brain, skin and liver. Inside the cells, the protein encoded from this gene is in the nucleolus, a small region within the core where ribosomes are; however, it is unclear whether the DCAF17 protein plays a role in this process.
They have identified at least 11 mutations in genes DCAF17 people with Woodhouse-Sakati syndrome. Some of these mutations correspond to: missense mutations (3), cutting and -splicing- mutations joint (3), small deletions (2) and insertions / deletions small (1). Most of these genetic mutations result in the synthesis of a protein that is abnormally short and rapidly decomposes or synthesis of a protein with impaired function. It is likely that loss of function of the protein DCAF17 is responsible for the characteristics of Woodhouse-Sakati syndrome, although it is unclear how this protein deficiency leads to hormonal abnormalities and other signs and symptoms of this disease.
Syndrome Woodhouse-Sakati is inherited as an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Woodhouse-Sakati, by complete PCR amplification of exons DCAF17 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).